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An Insight into Reprogramming Barriers to iPSC Generation

Stem Cell Reviews and Reports volume 16, pages 56–81 (2020)Cite this article

Abstract

Derivation of induced Pluripotent Stem Cells (iPSCs) by reprogramming somatic cells to a pluripotent state has revolutionized stem cell research. Ensuing this, various groups have used genetic and non-genetic approaches to generate iPSCs from numerous cell types. However, achieving a pluripotent state in most of the reprogramming studies is marred by serious limitations such as low reprogramming efficiency and slow kinetics. These limitations are mainly due to the presence of potent barriers that exist during reprogramming when a mature cell is coaxed to achieve a pluripotent state. Several studies have revealed that intrinsic factors such as non-optimal stoichiometry of reprogramming factors, specific signaling pathways, cellular senescence, pluripotency-inhibiting transcription factors and microRNAs act as a roadblock. In addition, the epigenetic state of somatic cells and specific epigenetic modifications that occur during reprogramming also remarkably impede the generation of iPSCs. In this review, we present a comprehensive overview of the barriers that inhibit reprogramming and the understanding of which will pave the way to develop safe strategies for efficient reprogramming.

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Acknowledgments

We thank all the members of the Laboratory for Stem Cell Engineering and Regenerative Medicine (SCERM) for their excellent support. This work was supported by North Eastern Region – Biotechnology Programme Management Cell (NERBPMC), Department of Biotechnology, Government of India (BT/PR16655/NER/95/132/2015) and also by IIT Guwahati Institutional Top-Up on Start-Up Grant. The authors sincerely apologize to all scientists whose research could not be cited in this review due to space restrictions.

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  1. Krishna Kumar Haridhasapavalan, Khyati Raina and Chandrima Dey contributed equally to this work.

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  1. Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India

    Krishna Kumar Haridhasapavalan, Khyati Raina, Chandrima Dey, Poulomi Adhikari & Rajkumar P. Thummer

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  1. Krishna Kumar Haridhasapavalan
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Haridhasapavalan, K.K., Raina, K., Dey, C. et al. An Insight into Reprogramming Barriers to iPSC Generation. Stem Cell Rev and Rep 16, 56–81 (2020). https://doi.org/10.1007/s12015-019-09931-1

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Keywords

  • induced Pluripotent Stem Cells
  • Cell reprogramming
  • Reprogramming barriers/roadblocks
  • Transcription factors
  • Epigenetics